P1276: HUMAN UMBILICAL CORD DERIVED MESENCHYMAL STROMAL CELL FOR THE TREATMENT OF STEROID-REFRACTORY AGVHD: A MULTICENTER, RANDOMIZED, DOUBLE-BLIND PHASE 2 TRIAL
Authors: Dai-Hong Liu, Chen Yao, Donglin Yang, Liping Dou, Xiaoqiang Hou, Kun Qian
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Failure of systemic corticosteroid therapy is quite common in patients with newly diagnosed acute graft-versus-host disease (aGVHD). Growing evidence has suggested that mesenchymal stromal cell (MSC) therapy could be a promising treatment option for aGVHD due to its distinctive immunomodulating functions. Aims: We evaluated the efficacy and safety of human umbilical cord derived MSCs in patients with grade II-IV, steroid-refractory aGVHD. Methods: This multicenter, randomized, double-blind, placebo-controlled phase II study (Chinese Clinical Trial Registry, ChiCTR2000035740) enrolled patients with grade II-IV, steroid-refractory aGVHD from 7 Chinese centers. Patients were randomized 1:1 to receive MSCs or placebo twice per week for 4 weeks, in addition to second-line therapy according to institutional standards. Patients who achieved partial response (PR) at day 28 were eligible to receive further infusions twice per week for additional 4 weeks. The primary endpoint is overall response rate (ORR) at day 28, which is defined as the proportion of patients achieving a CR or PR without the use of additional systemic therapies for aGVHD. The secondary endpoints included CR rate at day 28, ORR at day 56, CR rate at day 56, durable complete response rate (DCR), OS, ECOG score. The safety endpoints included adverse events (AE), serious adverse events (SAE) and infusion toxicity. Results: 78 patients with a median age of 38 (range, 13 to 62) years were enrolled in this trial from August 2020 to March 2022 and followed up to February 2023. The ORR at day 28 was 60.0% in MSC group (n = 40) and that in placebo group (n = 38) was 50% (odds ratio, 1.50; 95% CI, 0.61 to 3.68; p = 0.375; Figure 1). The ORR at day 56 was 50.0% in MSC group and 34.2% in placebo group (odds ratio, 1.92; 95% CI, 0.77 to 4.79; p = 0.158, Figure 1). 62 (79.8%) patients from the first three centers, which were highly consistent in the clinical routine, were analyzed. The ORR at day 28 was significantly higher in MSC group than in placebo group (71.9% vs. 46.7%; odds ratio, 2.92; 95% CI, 1.02 to 8.37; p = 0.043). The ORR at day 56 was 59.4% in MSC group and 40.0% in placebo group (odds ratio, 2.19; 95% CI, 0.79 to 6.05; p = 0.127). Among 25 patients with grade III-IV aGVHD, the ORR in the MSC group was also higher than that in the placebo group (61.5% vs. 33.3% at day 28; 53.9% vs. 25.0% at day 56), yet not statistically significant. In 42 patients with gastrointestinal involvement, the ORR at day 28 was significantly higher in MSC group than in placebo group (66.7% vs. 33.3%; odds ratio, 4.00; 95% CI, 1.11 to 14.43; p = 0.031). The incidences of adverse events and severe adverse events were comparable between these two groups. For both groups, the most common adverse events were leukopenia, thrombocytopenia and CMV-DNAemia. Summary/Conclusion: MSCs plus second-line treatment increase the overall response rate in steroid-refractory aGVHD and are well-tolerated. Patients with aGVHD, especially those involved in gastrointestinal tract, could benefit from MSC therapy as a second-line treatment.Keywords: Allogeneic hematopoietic stem cell transplant, Acute graft-versus-host disease, Mesenchymal stem cell, Clinical trial